The hypothesis of this research is that corrective reconstruction methods that incorporate an accurate model of the emission computed tomography (ECT) imaging process will significantly improve the quality and quantitative accuracy of ECT images and as a result, improve clinical diagnosis. The long term goal of the project is to develop corrective reconstruction methods for specific ECT imaging applications, to evaluate improvements in reconstructed image quality and quantitative accuracy, and to assess their clinical efficacy. In this renewal application that represents continued research for the 12th to 16th years, the applicants proposed to gradually wrap up earlier research in corrective single photon emission computed tomography (SPECT) reconstruction methods using low energy photons and its application in myocardial SPECT. The proposed new emphasis will be in tumor imaging using SPECT imaging with 67Ga and 111In agents which emit medium energy photons, and using the new dual-camera coincidence tomography (DCCT) method with 18F (a positron emitter with two 511 keV high energy photons) labeled fluorodeoxyglucose (FDG). The research would involve development of new corrective image reconstruction methods and detailed evaluation of the resultant reconstructed image in terms of quantitative accuracy, image quality, an clinical efficacy. The renewal grant application has five specific aims. In aim #1, the applicants proposed to investigate characteristics of SPECT imaging of 67Ga and 111In using medium energy collimators. In aim #2, they proposed to investigate the principles and characteristics of the DCCT imaging methods using 18F. Also, they would investigate methods to model these imaging characteristics. In aim #3, the applicants proposed to continue the development of accurate, robust and efficient three-dimensional (3D) and four-dimensional (4D) compensation methods for image degrading factors in both SPECT and DCCT. In aim #4, they proposed to evaluate the efficacy of the corrective reconstruction methods developed in aim #3 by computer simulation studies, experiments using physical phantoms, image quality indices, observer performance experiments and ROC analysis methods. Finally, in aim #5, the applicants proposed to evaluate the clinical efficacy of the corrective reconstruction methods in four patient studies. The applicants projected that the research could significantly improve tumor imaging using dual camera ECT systems operated in both single photon and coincidence detection modes.